Project Summary/Abstract Chronic pain is a major healthcare burden, representing economic costs of up to $635B per year, more than cancer, diabetes, and heart disease. Pain is a highly heterogeneous condition comprising neuropathic, nociceptive and inflammatory components, and patient responses to currently available drugs vary greatly. A very promising approach to target various forms of pain is through antagonism of key players in neuro-inflammation. Specifically, the chemokine receptor system, a complex network of over 20 different receptors and over 80 ligands, is integral to neuroinflammatory processes and the pharmaceutical industry had been very active in developing compounds targeting individual receptors in the network. However, the biological complexity, ligand promiscuity, and receptor redundancy of the chemokine receptor system has precluded successful clinical development of the compounds and many pharma have exited the pain therapeutic area. A major limitation of successful targeting of this network is sufficient understanding of the molecular and cellular dynamics of the chemokine network, and how specific receptors vary in chronic pain conditions. In a funded SBIR study, we aim to determine the genetic expression of a heterogenous chemokine receptor utilizing human clinical samples collected in a clinical trial evaluating a receptor antagonist. This application is to participate in i-Corps program at NIH.